A Brandeis University study published this week in Nature shows for the first time that a molecular signal maintains coherence among brain clock cells that regulate daily activity of Drosophila melanogaster (fruit flies). The two key groups of neurons control morning and evening activity and are maintained in synch even when the flies are plunged into darkness for extended periods of time.

This daily resetting signal flows from the morning to the evening cells and maintains a 12-hour difference between the timing of morning and evening activity, without the need for any environmental cues. The Brandeis researchers came to this conclusion by speeding up only the morning cell clock or only the evening cell clock. The results showed clearly that these two clocks always remained coupled in a network that was governed by the morning cell signal.

"We think it very likely that something similar is occurring in the brain of mammals, including humans, because their clock neurons also maintain remarkable coherence," said Professor Michael Rosbash, director of the National Center for Behavioral Genomics at Brandeis, and a Howard Hughes Medical Institute investigator. "However, circadian brain anatomy in mammals is much more complicated and the tools much too primitive to allow a similar network approach at this time. Flies are state-of-the art. Fortunately, their circadian clocks and even neural mechanisms are quite conserved with mammals."

"We were curious about how these brain cells stay synchronized, so we controlled the way time was ticking in individual clocks: we made the morning cells run faster and the evening cells relatively slower, and the other way around," explained researcher Dan Stoleru. "In this fashion, we introduced phase differences between them. It turned out that no matter the manipulation, the morning cells set the pace of the entire system, so that the rhythm always stayed on track."

The study showed that the morning clock resets the evening clock every day, without changing the intrinsic speed of the evening clock. Between daily resets, therefore, the evening cells time evening activity with their own clock, but they will always start counting time from the moment they were reset by the morning cells. In other words, the evening clock triggers the alarm at its own pace, but it is the morning clock which sets the alarm every day.

"So if you are looking over several days, only one period will be observed – the one dictated by the morning clock," Stoleru said.

Research by the same Brandeis team, published last year in Nature, had shown that two distinct groups of clock neurons determine morning and evening activity. The present study greatly advanced the understanding of how temporal coherence between these two cell groups, and between their behavioral outputs, is achieved.

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